DESCRIPTION: Chronic kidney disease (CKD) remains an unsolved challenge for the nephrologist, as it almost inevitably leads to end-stage renal failure, a life-threatening condition that necessitates renal replacement therapy. Current therapeutic strategies for the treatment of CKD include changes in life-style and/or medications to alleviate the underlying cause of disease. Since renal disease is typically diagnosed following significant scar formation, adjuvant strategies that oppose the molecular and cellular program of fibrosis that drives renal disease and activate matrix degrading pathways are urgently required. A preponderance of preclinical data in models of fibrotic renal disease speaks to the collagen catabolyzing activity of the naturally occurring peptide hormone Relaxin (H2R). Translation of these findings into clinical regimen has been painfully slow in large part due to the costs and logistical difficulties associated with commercial production of recombinant human H2R. To fully capitalize on the anti-fibrotic potential of H2R, Angion Biomedica Corp., NY and Chemical and Biopharmaceutical Laboratories (CBL, CO) have developed a library of H2R-like peptides in commercially viable quantities at a fraction of the cost associated with production of similar quantities of recombinant human H2R. Importantly, our preliminary studies suggest that these novel peptides share H2R-like bioactivity in vitro. The proposed SBIR Phase I program seeks to evaluate the activity of these H2R-like peptides in experimental CKD. Successful completion of the proposed work will enable us to enter a lead H2R-like peptide into a comprehensive SBIR Phase II program goals for which include developing clinically optimal strategies for peptide delivery, evaluation of lead peptide in CKD models with co-morbid disease and as adjuvant to standard-of-care and safety/toxicology profiling of lead peptide. PUBLIC HEALTH RELEVANCE: Chronic kidney disease is a major health and socioeconomic burden in the United States. Development of a clinically viable antifibrotic strategy against chronic kidney disease is of tremendous significance.